The present invention is directed to the provision of a dry powder formulation containing one or more active pharmaceutical ingredients (APIs) for the treatment of respiratory disorders such as asthma or COPD. A range of classes of medicaments have been developed to treat respiratory disorders and each class has differing targets and effects. A common feature of inhalable medicaments is that they must penetrate deep into the lung in order to reach their site of action.
To this end, the APIs are micronised, e.g. by jet milling, in order to obtain particles having the required size, typically a mass median aerodynamic diameter (MMAD) of 1-5 μm. The micronisation process imparts energy into the particles of the API, leading to fracture and particle size reduction. This process generates new surfaces which are high in energy and possess static charge. The energy imparted by the micronisation process may also lead to the introduction of amorphous character into the otherwise crystalline material of the API particles. These activated surfaces are generally regarded in the art as being undesirable, primarily because they have a tendency to absorb water leading to agglomeration of the API particles. This unpredictably detrimentally affects the particle size distribution of the API which in turn affects the amount of fine particles of API reaching the lungs, quantified by the fine particle fraction (FPF), as determined using an impactor.
Various post-micronisation techniques have been proposed to relax and equilibrate the powder prior to formulation in order achieve a more consistent performance (principally a consistent FPF). They typically involve exposing the micronised particles to a humid environment. See, for example, the discussion of this approach in Particulate Interactions in Dry Powder Formulations for Inhalation, X. M. Zeng et al., Taylor & Francis, London, 2000.
However, post-micronisation treatment adds to the complexity of the process and delays the manufacturing and packaging processes. There remains a need in the art for improved approaches.